Usher Sydrome typel (USH1) is characterized by a profound congenital sensoneural hearing loss, vestibular dysfinction and prepubescent onset retinitis pigmentosa. Family studies indicated that three genes with different chromosomal locations are responsible for USH1; a defect in any one of these genes causes the disease. Of these, the gene USH1B mapped to a region homologous to the murine region containing the mouse deafness mutant shaker-1 which results from mutations in myosin VIIa. Subsequent work confirmed that myosin VIIa is the cause of Usher Sydrome type 1B and localized the myosin VIIa protein to the receptor cells of the inner ear (Hasson et al. (1995) Genomics 36:431-439) and the connecting cilia of photoreceptor cells in the retina (Liu et al. (1997) Cell Motil. Cytoskel. 37:240-252).
Retinitis pigmentosa is also associated with Bardet-Biedl Syndrome. Bardet-Biedl Syndrome is further characterized by obesity, retinal degeneration, syndactyly and/or polydactyly, hypogenitalism and mental retardation (Schachat et al. (1982) Arch. Ophthalmol. 100:285-288; Green et al. (1989) N. Engl. J. Med. 321:1002-1009) and can result from aberrations in one of at least four different genes. Other publications relating to myosin IXa include Bruford et al. (1997) Genomics 41:93-99 and Bement et al. (1994) Proc. Natl. Acad. Sc. USA 91:6549-6553.
All references cited herein are incorporated by reference.